Florey researchers identify biomarker to predict sudden unexpected death in epilepsy

Sudden unexpected death in epilepsy (SUDEP) effects around 1 in 1,000 people living with epilepsy each year. New findings by Florey researchers involving a gene that effects cardiac dysfunction in SUDEP could lead to the development of novel biomarkers to identify those at risk.

SUDEP most frequently occurs in young adults with severe uncontrolled seizures. A clear understanding of what causes the condition remains elusive for scientists and clinicians.

The Florey’s Professor Chris Reid and Dr Ming Soh are working with clinical and research collaborators to uncover new ways to diagnose and manage SUDEP early on.

Their work builds on earlier scientific findings from collaborators of the team who identified a range of genetic changes, known as gene ‘variants’, in people who had passed away from SUDEP.

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In their latest research, the team probed to understand how variants in one of these genes, KCNH2, could affect the function of heart ion channels through which electrical messages flow to regulate heart rhythm. Variants in this gene, known as loss-offunction variants, were indeed causing dysfunction in the heart they confirmed.

“We discovered that loss-of-function KCNH2 variants play a more significant role in SUDEP than previously known. Common loss-of-function variants of this gene were expressed three times higher in a cohort who had experienced SUDEP compared to an epilepsy cohort who hadn’t. This increased to 11 times higher for rarer forms of the variant which disrupt function even more drastically,” said Dr Soh.

“We suspect what could be occurring before a SUDEP event is that the interruption of the heart’s electrical activity caused by variants in KCNH2 gene, combined with the impact of a seizure, may be causing the heart to stop beating,” she explained.

“These findings contribute a new piece to the puzzle in understanding the close connection between cardiac and brain factors that underlie SUDEP. Our discovery presents loss-of-function variants of the KCNH2 gene as possible predictive biomarkers for SUDEP which could be used therapeutically to identify those at risk of the condition,” said Prof Reid.

The team is now analysing how the brain and heart function at the time that SUDEP occurs using ECG-EEG animal models which they hope can be used to develop genetic screening tools and trial treatments to reduce SUDEP risk.

“This research is an incredible beacon of hope for people with epilepsy in the fight against SUDEP. Thank you to Dr Ming Soh and Prof Chris Reid for your tireless work. It's a monumental achievement and brings us one step closer to ending preventable deaths from epilepsy,” said Graeme Shears, CEO of the Epilepsy Foundation of Australia.

The research was made possible by philanthropic support, including from CURE Epilepsy, and funding by the Australian Government.